Overview: The whistleblower lawsuit alleging that Actos (pioglitazone) manufacturers underreported side effects has also implicated the role of Cleveland Clinic doctor, Steven Nissen; the complaint questions the doctor’s financial ties to the company and his pivotal role in presenting Actos as a safer alternative to Avandia. The qui tam suit, unsealed last month, claims that Takeda Pharmaceutical failed to report, among other things, cases of congestive heart failure (CHF) associated with the diabetes drug. In recent years, Actos’ safety has been questioned due to its association with bladder cancer.

The Actos whistleblower suit does not name Dr. Steven Nissen as a defendant, but states that financial ties should be investigated

In 2007, Dr. Nissen published a study showing that Avandia may increase the risk of heart attacks as much as 40%; the lawsuit states that the study was crucial in promoting Actos as a safer alternative to its sister drug

The suit was filed in June 2010 by Dr. Helen Ge, a former medical reviewer at Takeda, and unsealed this March. According to the complaint, Takeda failed to report cases of bladder and other cancers, heart problems, stroke, renal failure and suicidal ideation. Furthermore, the company allegedly told medical reviewers to omit cases of non-fatal cases of congestive heart failure as “serious”. Ge says she was fired after bringing up the issue with three of her superiors.

Nissen’s Study

Although the lawsuit only names Takeda as a defendant, it states that the role of Cleveland Clinic doctor Steven Nissen should be investigated. In 2007, Nissen and Kathy Wolski published a study showing that Avandia (rosiglitazone) may increase the risk of heart attacks by 43 percent; the drug subsequently came under fire. Ge’s complaint points out that his research was instrumental in positioning Actos as a safer alternative to Avandia, when it may actually be more dangerous. The lawsuit also notes that he was in charge of the PERISCOPE trials, which screened participants for the famous Avandia study. Takeda funded the trials for an estimated $8 to 10 million, with Cleveland Clinic receiving more than $13 million in revenue. These factors, the lawsuit states, “should be considered by analyzing Actos’ risks compared with Avandia’s.”

Nissen has denied the allegations, pointing out that the clinic’s revenue is unrelated to Ge’s claims. He has dismissed Ge’s claims as “total nonsense”, according to Heartwire. As for Takeda’s financing the PERISCOPE trials, Nissen says that this information was already disclosed, telling Heartwire that “there is nothing there that has not already been in the public domain for years.”

Background: Actos Bladder Cancer Risk

The U.S. Food and Drug Administration (FDA) approved Actos in July 1999 for treating patients with type 2 diabetes. In August 2007, the FDA issued a “black box” warning for Actos and Avandia to include the risk of exacerbating heart failure. At the time, Avandia was thought to pose a greater threat than Actos. By 2008, Actos was the 10th best-selling drug in the US, and had worldwide sales reaching $4.6 billion.

Last June, Actos was banned in France and Germany after a study funded by the French Medicines Agency linked the drug to an increased risk of bladder cancer. Shortly afterward, the FDA updated the safety label to include this risk. Recently, Canadian regulators made a similar label change. Takeda currently faces over 10,000 lawsuits alleging Actos causes bladder cancer.